Journal of Pharmaceutical Science and Application

Volume 3, Issue 1, Page 40-49, June 2021

E-ISSN : 2301-7708

A REVIEW OF PHYTOCHEMICAL AND PHARMACOLOGICAL

STUDIES OF Piper retrofractum Vahl.

Ni Komang Sri Lumbung Artha Wardani1, Ni Putu Eka Leliqia1*

1
Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Udayana University

Corresponding author email: eka_leliqia@unud.ac.id

ABSTRACT
Background: Javanese long pepper (Piper retrofractum Vahl.) is a plant that commonly found
in Southeast Asia and is empirically used to treat various diseases. It is known that the
phytochemical content in plants is one factor responsible for its pharmacology activities. The
study of the pharmacological effects of herbal ingredients both pre-clinically and clinically is
an attempt to prove their empirical properties. Aims: This review article aims to provide
information to academics and the public regarding phytochemical studies and pharmacological
activity that have been carried out regarding the Javanese long pepper plant. Methods: Article
preparation was carried out through literature studies from various national scientific journals,
international journals, and online reference books. Javanese long pepper data search system was
based on chemical content and pharmacological activity studies either in vitro, in vivo, or
clinical trials. Results: Phytochemical studies have shown that the plant parts of Javanese long
pepper contain compounds such as alkaloids, saponins, tannins, flavonoids, steroids,
triterpenoid, and glycosides. Based on studies of its pharmacological activity, Javanese long
pepper has been reported to have antimicrobial, antioxidant, cytotoxic, analgesic, androgenic,
aphrodisiac, antihyperlipidemic, antihyperuricemic, lowering leukocyte count, antileishmanial
and immunostimulant effects. Conclusion: The efficacy of Javanese long pepper has been
scientifically proven to have pharmacological effects either through in vitro or clinical studies
which can be taken into consideration for the development of traditional medicinal products.

Keywords: Javanese Long Pepper, Piper retrofractum, Phytochemical, Pharmacology activity

INTRODUCTION
Currently, people tend to change their
lifestyle towards a “back to nature”.
Globally, people are starting to use
traditional herbal medicines to maintain
their health. There are 40,000 types of
medicinal plants that have been known in
the world, and 30,000 of them are found in
Indonesia. Based on this, 90% of medicinal
plants are found in the Asian region[1]. The
Javanese long pepper plant (Piper
retrofractum Vahl.) is one of the herbal
ingredients that can be developed into
traditional medicinal products in Indonesia.
Javanese long pepper has long been
known as a plant that is widely used as
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traditional medicine. This plant is native to
Southeast Asia and is known as
hihatsumodoki in Japan. These plants are
widely cultivated in Indonesia and
Thailand[2]. Javanese long pepper in
Indonesia are found in Java, Sumatra, Bali,
Nusa Tenggara, and Kalimantan, where the
main production center of this plant is on
Madura[3].
The Javanese long pepper plant is
closely related to the pepper plant and is
included in Piperaceae family[4]. The
taxonomy of Javanese long pepper, namely
kingdom plantae; magnoliphyta division;
magnoliopside class; piperales order;
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 Wardani and Leliqia
piperaceae family; piper genus; and the
species Piper retrofractum[5]. Based on its
morphology, Javanese long pepper is a
climbing plant. The leaves are round,
lanceolate, and wide; green to dark green.
The fruit has varying shapes and sizes
ranging from small lengths (cylindrical),
flat length (filiform), elliptical (conical),
and short round (globular). The stem is
round and large; has a diameter of ± 5-7 cm;
length of the main stem 2.93-9.82 cm; The
color of the stem varies greatly from black,
brown to blackish brown[6].
Traditionally, the Javanese long pepper
plant is used for the treatment of digestive
function disorders, asthma, hypertension,
influenza, and for treating flatulence[7].
Based on its empirical properties, many
studies have been carried out related to the
pharmacological effects of Piper
retrofractum plants. Several studies
revealed that the phytochemical contained
in this plant has pharmacological activities,
including antimicrobial[8], antioxidant[9],
cytotoxic[10], analgesic[11], androgenic[12],
aphrodisiac[13], antihyperlipidemic[14],
antihiperuricemia[15], reducing the number
of leukocytes[16], antileishmanial[17], and
immunostimulants[18].
The increasing number of scientific
studies regarding the phytochemical
content and pharmacological activities of
Javanese long pepper is expected to provide
information to the public about the potential
of this plant as a traditional medicine. In
addition, this article can be used by
researchers as a consideration in developing
Javanese chili research for the treatment of
diseases.
METHODS
The method used in this review article
was a literature study. Literature was
collected from original articles published in
national and international scientific journals
online through searches on the Scopus
portal and Google Scholar. Literature can
also be in the form of a reference book. The
main keyword used is the name of the plant
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Volume 3, Issue 1, Page 40-49, June 2021
Piper retrofractum, then it is further
selected to obtain data related to its
phytochemical content and
pharmacological activity.
RESULTS AND DISCUSSIONS
Javanese long pepper (Piper
retrofractum Vahl.) are known to have
pharmacological activities. The type of
chemical content of this plant plays an
important role in determining its
pharmacological effect. Phytochemical
screening and isolation of chemical
compounds from Javanese long pepper is
one way to obtain information about the
chemical content and isolate compounds.
The pharmacological effect of an herbal
ingredient can be determined through
preclinical tests which include in vitro and
in vivo testing, as well as through clinical
trials. In vitro testing is carried out to
determine the efficacy of these herbal
ingredients so that they can predict and
determine the mechanism of the compound
to work with target receptors. This test is
carried out outside the body of a living thing
such as in bacterial cultures, isolated cells,
or isolated organs. In vivo testing is carried
out to see the behavior of the test animals so
that they can provide information about
their biological system after being given the
test material[19]. According to BPOM RI
(2015), clinical trials are studies using
humans as subjects to find or confirm
clinical, pharmacological and/or other
pharmacodynamic effects, and/or
identifying any unwanted reactions, and/or
studying absorption, distribution,
metabolism and excretion to ensure the
safety and/or effectiveness of the product
studied[20].
Chemical Content
The fruit, leaves, stems, and roots of
Javanese long pepper contain alkaloids,
saponins, tannins, flavonoids, steroids,
triterpenoid, and glycosides[21]. The results
of phytochemical screening conducted by
Krisnawan et al. (2017), showed that the
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 Wardani and Leliqia
aqueous extract of Javanese long pepper
leaves positively contained flavonoids and
saponins[22]. Yuliatmoko and Febria (2018)
also reported that dried leaves of Javanese
long pepper contain terpenoid
compounds[23]. Research by Insanu et al.,
(2017) revealed that Javanese long pepper
leaf extract contains flavonoids, tannin,
quinone, and steroid/triterpenoid
compounds[24].
Several studies had been succeeded in
isolating the chemical compounds from
Javanese long pepper. This plant is known
to contain piperine, chavicin, palmatic acid,
tetrahydropiperic acid, 1-undecylenyl-3, 4-
methylledioxy benzene, piperidine,
essential oils, N-isobutyldeka-trans-4-
dienamid, and sesamin[4]. Jamal et al.,
(2013) reported that there are 4 main
components of the essential oil of Javanese
long pepper leaves, namely germacrene D
(24.20%), tetramethylcyclo [5.3.1.0 (4.11)]
undec-8-ene (17.73%), Ar-turmerone
(11.55%) and benzyl benzoate (6.28%).
Meanwhile, 3 other sesquiterpene, namely
α-cubebene (3.55%), β-cubebene (2.59%),
and β-cadinene (2.49%) as well as
sesquiterpene alcohol curlone (2.67%) and
derivatives of phenyl propanoate, 2-
methoxy-4- (2-propenyl) –phenol (2.05%)
showed a content between 2-4%[8].
Amad et al., (2016) also stated that
other compounds have been isolated from
Javanese long pepper fruit, namely
piperine, methyl piperate, sylvatin, and
piperlonguminine[25]. According to the
findings reported by Bodiwala et al. (2007),
there are 3 compounds produced by n-
hexane and methanol extracts from the stem
of Javanese long pepper. The results of the
isolation showed that the n-hexane extract
of Javanese long pepper stems contained
sesamin (lignans) and pellitorine (amide)
compounds. Meanwhile, methanol extract
contains piplartine (amide) compounds[17].
Antimicrobial Activity
The leaves of Javanese long pepper are
known to have antibacterial activity as
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shown by a study conducted by Jamal et al.,
(2013). The activity test was carried out in
vitro with the diffusion method to see the
inhibitory diameter and the dilution method
to determine the value of the minimum
inhibitory concentration (MIC) of the test
sample against bacteria. The results showed
that essential oils with a concentration of
50% proved to have antibacterial activity
against Bacillus subtilis (NBRC 3134),
Micrococcus luteus (NBRC 14218),
Staphylococcus aureus (NBRC 14276) with
an inhibitory diameter of 8.5; 8.0; and 9.7
mm; but it had no effect on Eschericia coli
(NBRC 14237). It is also known that the
essential oil from the leaves of Javanese
long pepper has a MIC value of 2% (v/v)
against B. subtilis. Tetramethylcyclo
[5.3.1.0 (4.11)] undec-8-ene, germacrene
D, Ar-turmerone, and benzyl benzoate were
known as main components of essential oils
contained in Javanese long pepper leaves in
this study. Cell leakage testing and
observation by Scanning Electron
Microscopy (SEM) were carried out on B.
subtilis. Exposure of B. subtilis bacterial
cells with essential oil of Javanese long
pepper leaves at a concentration of 2% and
4% caused cell leakage of cellular
metabolites such as proteins and nucleic
acids, as well as ions from metals (K+ and
Ca2+). SEM observations showed that there
were morphological changes in these
bacterial cells[8]. Gauthier (2006) explains
that the leak is thought to affect changes in
bacterial morphology that can inhibit cell
wall synthesis. Ion leakage is caused by
damage to cell membranes and increased
membrane permeability. Damage to the cell
membrane will make it easier for organic
acids to penetrate the cytoplasmic
membrane and cause changes in membrane
stability which eventually leads to ion
leakage[26].
Panphut et al., (2020) reported that
Javanese long pepper fruit which were
extracted with several solvents such as
acetonitrile, methanol n-hexane,
isopropanol, and dichloromethane had
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 Wardani and Leliqia
antimicrobial activity with a range of
inhibition zone diameters 0.5–8.0 mm. The
acetonitrile extract showed antimicrobial
activity against E. coli, B. subtilis,
Enterococcus faecalis, Klebsiella
pneumoniae, Pseudomonas aeruginosa,
Salmonella typhi, S. aureus, Vibrio
parahaemolyticus XN89, Vibrio
paraparahaemolyticus 5HP, and Candida
albicans with MIC values of 36.0; 71.50;
4,50; 143.50; 143.50; 9.0; 71.50; 71.50;
71.50; and 1.0 mg/mL. Methanolic extract
also showed antimicrobial activity against
E. coli, B. subtilis, E. faecalis, K.
pneumoniae, P. aeruginosa, S. typhi, S.
aureus, V. parahaemolyticus XN89, V.
paraparahaemolyticus 5HP, and C.
albicans with MIC value of 22.50; 5,50;
45.0; 90.0; 179.50; 11.0; 45.0; 45.0; 22.50;
0.50 mg/mL. The n-hexane extract only
showed activity against C. albicans with a
MIC value of 2.50 mg/mL. Isopropanol
extract showed antimicrobial activity
against E. coli, B. subtilis, E. faecalis, S.
typhi, S. aureus, V. parahaemolyticus
XN89, V. paraparahaemolyticus 5HP, and
C. albicans with MIC values of 18.0; 9.0;
71.50; 9.0; 35.50; 71.50; 18.0; and 10.0
mg/mL; and dichloromethane extracts
showed antimicrobial activity against E.
coli, B. subtilis, E. faecalis, S. typhi, S.
aureus, V. parahaemolyticus XN89, V.
paraparahaemolyticus 5HP, and C.
albicans with MIC values of 80.0; 80.0;
40.0; 10.0; 80.0; 80.0; 40.0; and 18.0
mg/mL. Based on this study, it is known
that the bioactive compound Javanese long
pepper which was extracted with methanol
had better potential against pathogenic
microorganisms[27].
The results of research conducted by
Krisnawan et al. (2017), reported that the
aqueous extract of Javanese long pepper
leaves various concentrations also had
antibacterial activity against S. aureus. The
extract with a concentration of 20%, 35%,
50%, 65%, and 80% had an inhibitory
diameter of 1.40 mm; 2.38 mm; 2.88 mm;
2.76 mm; 4.49 mm respectively. Based on
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these results, aqueous extract with a
concentration of 20-65% were categorized
as having weak activity, while aqueous
extract with a concentration of 80% was
categorized as having moderate activity[22].
Pan et al., (2009) stated that there are three
categories of inhibitory power, the weak
activity with an inhibition diameter of 0 mm
– 3mm, a moderate activity with an
inhibition diameter of 3 mm – 6 mm and the
third category is strong with an inhibition
diameter of > 6 mm[28].
Amad et al., (2016) revealed that
Javanese long pepper fruit had an anti-
tuberculosis effect. In vitro testing on the
bacterium Mycobacterium tuberculosis
strain H37Ra showed that the methanol
extract and the isolates contained therein,
namely piperlonguminine and piperine, had
antibacterial activity. The MIC value of the
methanol extract was 25 µg/mL, while
piperlonguminine and piperine had weaker
activity with MIC values of 50.0 µg/mL.
Two other compounds that have also been
isolated from methanol extract, namely
sylvatine and methyl piperate, did not have
antibacterial activity[25].
Antioxidant Activity
Based on research conducted by Jadid
et al. (2016), Javanese long pepper that was
extracted with several solvents had
antioxidant activity. The activity was
determined using using DPPH method. The
IC50 value obtained from the n-hexane
extract was 57.66 μg/mL; ethyl acetate of
66.12 μg/mL; and methanol 101.74 μg/mL.
In this study, the antioxidant activity was
classified into 3 categories. Strong
antioxidant activity had a range of IC50
values of 10-50 μg/mL; moderate
antioxidants have an IC50 value range of 50-
100 μg/mL, and weak antioxidants have IC
values >100 µg/mL. Based on these
categories, n-hexane and ethyl acetate
extracts were classified as antioxidants with
moderate activity, while methanol extracts
were classified as weak antioxidants[9].
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 Wardani and Leliqia
Mulia et al., (2016) conducted a study
comparing the antioxidant activity of
Javanese long pepper fruit extracts from
Pamekasan and Karangasem. The results
showed that samples from Pamekasan had
weaker antioxidant activity (IC50 288.037
μg/mL) than samples from Karangasem
(IC50 285.61 μg/mL). However, based on
the IC50 value, the antioxidant activity of
both samples is still relatively weak[29].
Cytotoxic Activity
Javanese long pepper extract has been
shown to have a cytotoxic activity against
Artemia salina Leach shrimp larvae, MCF-
7 breast cancer cells, HeLa cell line
(continuous cell line derived from cervical
cancer epithelial cells), T47D breast cancer
cells and lung cancer cells (SCLC-H22 and
NCI-H187). According to findings reported
by Clarasati et al., (2016), extract and
fractions of Javanese long pepper fruit had
cytotoxic activity against Artemia salina
Leach shrimp larvae. The LC50 value of
95% ethanol extract, n-hexane fraction,
ethyl acetate fraction, and aqueous fraction
were 44.05 μg/mL; 70.79 μg/mL; 79.43
μg/mL; and 112.2 μg/mL respectively.
Extracts and fractions of Javanese long
pepper were stated to have cytotoxic
activity because they had an LC50 value
lower than 1,000 μg/mL[10].
Mulia et al., (2016) reported that
Javanese long pepper fruit extract from
Karangasem and Pamekasan had cytotoxic
activity against MCF-7 breast cancer cells.
The treatment of various concentrations of
Javanese long pepper extract from the two
regions were able to have effect on these
cells. There was a decrease in the IC50 value
with increasing concentration. Samples
from Karangasem and Pamekasan had
cytotoxic activity with IC50 values of
63.283 μg/mL and 83.662 μg/mL. Based on
these data, the cytotoxic activity of both
samples is classified as active because the
IC50 value is in the 50-100 μg/mL range[29].
Hasan et al. (2016) also researched on
MCF-7 breast cancer cells that was exposed
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to 70% ethanol extract of Javanese long
pepper fruit from various regions in
Indonesia. The results of the cytotoxic test
on MCF-7 breast cancer cells showed that
the extracts from Paranggupito 1 (Central
Java), Paranggupito 2 (Central Java),
Girintontro (Central Java), Air Naningan 1
(Lampung), and Air Naningan 2 (Lampung)
had a value IC50 successively 80.43;
126.09; 181.52; 54.35; 4.35 μg/mL. These
results indicate that the Javanese long
pepper from Air Naningan 2 have the best
cytotoxic activity. Further testing on MCF-
7 breast cancer cells given the extract from
Air Naningan 2 with a concentration of 250
μg/mL showed that the cancer cells were
severely damaged[30].
Based on research conducted by
Ekowati et al. (2011), it is known that 96%
ethanol extract of Javanese long pepper fruit
had cytotoxic activity against HeLa cells
with an IC50 value of 47.409 µg/mL and
against T47D with an IC50 value of 92.38
µg/mL. Ekowati et al., (2011) also
combined this extract with red ginger
rhizome. The results showed increased
cytotoxic activity against HeLa and T47D
cells when the two ingredients were
combined, with smaller IC50 values for the
two test cells, namely 33 µg/mL and 53
µg/mL.[31] Compound that role play in the
cytotoxic activity of this plant is piperine
(alkaloid group). The piperin can protect
cells from cancer by binding to proteins in
mitochondria and triggering apoptosis
without damaging normal cells, through
increased activity of antioxidant enzymes
such as superoxide dismutase, catalase, and
glutathione peroxidase. In addition,
piperine can inhibit NFkB so that it can
prevent tumor formation through TNF-α
and inhibit the angiogenesis process[32,33].
Amad et al., (2016) reported that the
methanol extract of Javanese long pepper
fruit and their isolates (piperine and
piperlonguminine) had cytotoxic activity
against lung cancer cells [SCLC-H22 and
NCI-H187 (ATCC CRL-5840)]. The
cytotoxic activity can be shown based on
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 Wardani and Leliqia
the percentage value of the growth
inhibition of the test cells. The methanol
extract of Javanese long pepper with a
concentration of 5 µg/mL also had a %
inhibitory value of SCLC-H22 and NCI-
H187 lung cancer cells of 38.83 and
96.71%, respectively. Piperine with a
concentration of 25 µg/mL had a %
inhibitory value against SCLC-H22 and
NCI-H187 lung cancer cells of 7.68 and
15.58%, respectively. Meanwhile,
piperlonguminine with a concentration of
25 µg/mL had a % inhibitory value against
SCLC-H22 and NCI-H187 lung cancer
cells of 11.59 and 15.04%. The IC50 value
was only obtained in the methanol extract
of 20.98 µg/mL against NCI-H187[25].
Analgesic
Evacuasiany et al., (2010) revealed that
the ethanol extract of Javanese long pepper
fruit at a dose of 3 g/kg BW given to mice
orally had analgesic activity equivalent to
acetosal at a dose of 0.42 g/kg BW. The
ethanol extract at doses of 0.75 g/kg BW
and 1.5 g/kg BW also showed analgesic
activity but this activity was still weaker
than acetosal. The analgesic effect is
thought to be due to decreased
prostaglandin synthesis so that inhibit
sensitivity to pain responses[11].
Androgenic
Based on research conducted by
Moeloek et al., (2010), the fruit extract of
Javanese long pepper had androgenic
activity that has been tested clinically. The
100 mg/day extract given to several male
hypogondism patients for 60 days had an
androgenic effect. Its effect was indicated
by an increase in testosterone levels in 78%
of the total number of patients (9 patients).
However, the androgenic effect of the
extract was categorized as weak androgenic
because it was unable to significantly
reduce follicle stimulating hormone and
luteinizing hormone levels (p <0.05)[12].
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Aphrodisiac
Tominik (2018) examined the
aphrodisiac effect of the Javanese long
pepper fruit extract. The administration of
extract at a dose of 210 mg/kg BW to albino
mice (Mus musculus) for 36 days was able
to increase diameter of the seminferus
tubule, the weight of the testis, the core
Leydig diameter, the thickness of the
germinal seminiferous tubular epithelium,
Sertoli cells, the Leydig cell count, the
spermatogenesis index, and the associate
cell significantly (p<0.05). The increase in
spermatogenic cells is thought to be due to
an increase in metabolism in the body. This
causes an increase in energy for protein
synthesis which affects the spermatogenesis
process when mitotic division increases[13].
According to findings reported by
Rahmawati and Bachri (2012), an infusion
that contained combination of Piper
retrofractum at a dose of 210 mg/kg BW,
Centella asiatica at a dose of 546 mg/kg
BW, and Curcuma domestica at a dose of
910 mg/kg BW gave aphrodisiac effect to
male rats. This infusion was orally
administered for 7 days simultaneously.
The effect was indicated by sexual behavior
intensity (introduction, coitus and climbing
frequency). The male rat that was given an
infusion had higher sexual behavior
intensity than control group significantly
(p<0.05). This is thought to be due to the
piperine content of Javanese long
pepper[34]. Muslichah (2011) also reported
that the piperine content of the Javanese
long pepper fruit extract at a dose of 1.6
mg/kg BW and an insoluble fraction of n-
hexane free of piperine from javanese long
pepper fruit at a dose of 29.10 mg/kg BW
which given to male rats for 27 days orally
had an aphrodisiac effect[35].
Antihyperlipidemia
Based on research conducted by
Mustofa et al. (2014), the ethanol extract of
97% Javanese long pepper fruit had the
potential to be an antihyperlipidemic. This
was indicated by the ability of this extract
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 Wardani and Leliqia
to influence the lipid profile and histology
of the coronary arteries of male white rats
(Rattus norvegicus) which were given a
high-fat diet for 49 days orally. In the
negative control group, the treatment of a
high-fat diet in the test animals showed an
increased lipid profile of total cholesterol,
Low Density Lipoprotein (LDL) and
triglyceride levels and significantly
decreased High Density Lipoprotein (HDL)
compared to normal controls (p<0.05). In
addition, a high-fat diet also causes the
intactness of endothelial cells and can even
be found atherosclerotic plaques
accompanied by thickening of the aortic
wall. Meanwhile, in the treatment group
where the test animals were given a high-fat
diet along with the extract at a dose of 40
mg/kg BW showed a decrease in total
cholesterol, LDL and triglyceride levels as
well as a significant increase in HDL levels
compared to negative controls (p<0.05). In
the histology of the coronary arteries, it
showed that the endothelial cells were intact
but not atherosclerotic plaques are formed
on the walls of the blood vessels[14].
Antihyperuricemia
Fitriani et al. (2018), tested the
antihyperuricemia activity of herbal
combination containing Javanese long
pepper fruit, broadleaf plantain (Plantago
major), and celery (Apium graveolens).
Administration of this combination at a
dose of 2 g/kg BW to male white rats for 7
days orally, were able to reduce uric acid
levels. Flavonoids were thought to be
responsible for this activity[15]. In addition,
this study also reported that giving these
herbs at doses of 2, 3, 4, and 5 g/kg BW had
no effect on kidney function and liver
function tested on white rats for 14 days[36].
Decreased Number of Leukocytes
A research by Nurhidayah et al., (2019)
revealed that the methanol extract of
Javanese long pepper fruit with a
concentration of 100% given topically was
effective in reducing the number of
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leukocytes in Wistar rats with traumatic
ulcers. Piperine was thought to be an active
compound that plays a role in its activity.
Piperine is known to stimulate salivary
flow, where an increase in salivary pH can
affect the increase in buffer activity in
saliva. In addition, piperine is thought to aid
in the healing process of lesions because it
has antipyretic, analgesic, antifungal, and
antibacterial properties[35].
Antileishmanial
Bodiwala et al., (2007) reported that
some extracts of Javanese long pepper stem
had antileishmanial activity which was
tested in vitro against Leismania donovani
promastigotes. The IC50 values of acetone,
ethyl acetate, n-hexane, and methanol
extracts were 3.5; 45; 5; 7.5 µg/mL. In this
study also obtained 3 isolates from the
extract of n-hexane and methanol. The
results of the isolation showed that the n-
hexane extract contained sesamin and
pellitorin. While the methanol extract
contained piplartine. Further testing of the
isolates showed that only piplartine was
known to be active and gave an IC50 value
of 7.5 µM. Antileishmanial was also carried
out in vivo using infected hamsters by
observing the amastigotes of Leismania
donovani. Piplartine at a dose of 30 mg/kg
BW given intra-peritoneally for 10 days
significantly reduced the spleen parasitic
burden and spleen weight (P <0.05)[16].
Immunostimulants
According to the findings reported by
Roseno et al. (2019), it is known that the
ethanol extract of Javanese long pepper fruit
at a dose of 280 mg/kg BW given to test
animals orally for 6 days has
immunomodulatory activity as an
immunostimulant. In this case, the
immunostimulant activity of Piper
retrofractum extract had a higher
phagocytosis index value compared to the
comparison group of phytopharmaca
immunostimulants of 1.5x; and able to
increase peripheral blood neutrophil levels
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 Wardani and Leliqia
which play an important role in the process
of phagocytosis[36].
CONCLUSION
Based on the results of phytochemical
studies, the Javanese long pepper plant
(Piper retrofractum Vahl.) contains
phytochemical compounds of alkaloids,
flavonoids, essential oils, saponins,
terpenoids, tannins, quinones,
steroids/triterpenoids, lignans and amides.
Javanese long pepper has also been shown
to have pharmacological effects either
through in vitro, in vivo, or clinical studies.
Activities that have been tested in vitro
were antimicrobial, antioxidant, and
cytotoxic; activities that have been tested in
vivo are analgesic, aphrodisiac,
antihyperlipidemic, anti-hyperuricemia,
and decreased leukocyte count; The activity
which has been tested in vitro and in vivo
was antileishmanial; The activity that has
been clinically tested was androgenic.
These activities are inseparable from the
chemical content in the Javanese long
pepper.
CONFLICT OF INTEREST
In the preparation of this article, there
is no conflict or interest. This article is
written independently without the
involvement of other parties who could
improperly influence this article.
ACKNOWLEDGEMENT
Thank you to all parties, especially
from the Pharmacy Study Program of the
Faculty of Mathematics and Natural
Sciences, Udayana University who have
provided a lot of assistance in the process of
making this article.
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